Smoking, alcohol, overnutrition and a high red meat and low folate, fiber and calcium diet have been associated with colorectal cancer (CRC) and adenoma. Past work, including ours, suggests the importance of the modifying effects of genetic susceptibility factors on most of these associations. Our investigation of the rapid rise in CRC risk among Japanese migrants to Hawaii suggests that Japanese may be more genetically susceptible to the carcinogenic effects of red meat and processed meat, compared to whites, and that they may be particularly protected by a high folate intake. These results are entirely consistent with the sharp rise in CRC incidence observed in Japan over the last 30 years, presumably as a result of the westernization of the diet. However, we have identified another population of Japanese migrants in Sao Paulo, Brazil, for whom CRC rates have remained low, compared to Japanese in Japan an Hawaii, despite a high fat and red meat intake and an affluent western lifestyle. Because this anomaly might provide critical information about protective factors for CRC, we are seeking funding to conduct a colonoscopy-based case- control study of adenoma among Japanese Brazilians in Sao Paulo and to compare findings with our on- going adenoma study (CA 72520) in Hawaii Japanese (565 cases, 660 controls) and with a third (separately funded) companion study (800 cases, 800 controls) conducted in Tokyo. In Sao Paulo, a lifestyle questionnaire will be administered in-person to 550 adenoma cases and 550 endoscopically normal controls matched on age, sex, hospital and date of colonoscopy. In addition to estimating the total intake of energy, nutrients and other dietary components, consumption of meat and fish prepared by high-temperature methods and doneness of meat will be assessed. A blood sample will also be stored for the future testing of exposure markers and genes related to growth hormones, insulin resistance, carcinogen bioactivation and folate metabolism which are being assessed in the Hawaii and Tokyo studies. [unreadable] [unreadable] [unreadable]